Analysis of Prognostic Factors and Surgical Management of Elderly Patients with Low-Grade Gliomas

World Neurosurg. (2023) 176:e20-e31

The number of elderly patients with low-grade glioma (LGG) is increasing, but their prognostic factors and surgical treatment are still controversial. This paper aims to investigate the prognostic factors of overall survival and cancer-specific survival in elderly patients with LGG and analyze the optimal surgical treatment strategy.

METHODS: Patients in the study were obtained from the Surveillance, Epidemiology, and End Results database and patients were randomized into a training and a test set (7:3). Clinical variables were analyzed by univariate and multivariate Cox regression analysis to screen for significant prognostic factors, and nomograms visualized the prognosis. In addition, survival analysis of elderly patients regarding different surgical management was also analyzed by Kaplan-Meier curves.

RESULTS: Six prognostic factors were screened by univariate and multivariate Cox regression analysis on the training set: tumor site, laterality, histological type, the extent of surgery, radiotherapy, and chemotherapy, and all factors were visualized by nomogram. And we evaluated the accuracy of the nomogram model using consistency index, calibration plots, receiver operator characteristic curves, and decision curve analysis, showing that the nomogram has strong accuracy and applicability. We also found that gross total resection improved overall survival and cancer-specific survival in patients with LGG aged ‡65 years relative to those who did not undergo surgery (P < 0.001).

CONCLUSIONS: Based on the Surveillance, Epidemiology, and End Results database, we created and validated prognostic nomograms for elderly patients with LGG, which can help clinicians to provide personalized treatment services and clinical decisions for their patients. More importantly, we found that older age alone should not preclude aggressive surgery for LGGs.

Transforaminal Lumbar Interbody Fusion Versus Posterolateral Fusion Alone in the Treatment of Grade 1 Degenerative Spondylolisthesis

Neurosurgery 93:186–197, 2023

Transforaminal lumbar interbody fusion (TLIF) and posterolateral fusion (PLF) alone are two operations performed to treat degenerative lumbar spondylolisthesis. To date, it is unclear which operation leads to better outcomes.

OBJECTIVE: To compare TLIF vs PLF alone regarding long-term reoperation rates, complications, and patient-reported outcome measures (PROMs) in patients with degenerative grade 1 spondylolisthesis.

METHODS: A retrospective cohort study using prospectively collected data between October 2010 and May 2021 was undertaken. Inclusion criteria were patients aged 18 years or older with grade 1 degenerative spondylolisthesis undergoing elective, single-level, open posterior lumbar decompression and instrumented fusion with ≥1-year follow-up. The primary exposure was presence of TLIF vs PLF without interbody fusion. The primary outcome was reoperation. Secondary outcomes included complications, readmission, discharge disposition, return to work, and PROMs at 3 and 12 months postoperatively, including Numeric Rating Scale-Back/Leg and Oswestry Disability Index. Minimum clinically important difference of PROMs was set at 30% improvement from baseline.

RESULTS: Of 546 patients, 373 (68.3%) underwent TLIF and 173 underwent (31.7%) PLF. Median follow-up was 6.1 years (IQR = 3.6-9.0), with 339 (62.1%) >5-year follow-up. Multivariable logistic regression showed that patients undergoing TLIF had a lower odds of reoperation compared with PLF alone (odds ratio = 0.23, 95% CI = 0.54-0.99, P = .048). Among patients with >5-year follow-up, the same trend was seen (odds ratio = 0.15, 95% CI = 0.03-0.95, P = .045). No differences were observed in 90-day complications (P = .487) and readmission rates (P = .230) or minimum clinically important difference PROMs.

CONCLUSION: In a retrospective cohort study from a prospectively maintained registry, patients with grade 1 degenerative spondylolisthesis undergoing TLIF had significantly lower long-term reoperation rates than those undergoing PLF.

Rehemorrhage of brainstem cavernous malformations: a benchmark approach to individualized risk and severity assessment

J Neurosurg 139:94–105, 2023

Brainstem cavernous malformations (BSCMs) represent a unique subgroup of cavernous malformations with more hemorrhagic presentation and technical challenges. This study aimed to provide individualized assessment of the rehemorrhage clustering risk of BSCMs after the first symptomatic hemorrhage and to identify patients at higher risk of neurological deterioration after new hemorrhage, which would help in clinical decision-making.

METHODS A total of 123 consecutive BSCM patients with symptomatic hemorrhage were identified between 2015 and 2022, with untreated follow-up > 12 months or subsequent hemorrhage during the untreated follow-up. Nomograms were proposed to individualize the assessment of subsequent hemorrhage risk and neurological status (determined by the modified Rankin Scale [mRS] score) after future hemorrhage. The least absolute shrinkage and selector operation (LASSO) regression was used for feature screening. The calibration curve and concordance index (C-index) were used to assess the internal calibration and discrimination performance of the nomograms. Cross-validation was further performed to validate the accuracy of the nomograms.

RESULTS Prior hemorrhage times (adjusted OR [aOR] 6.78 per ictus increase) and Zabramski type I or V (OR 11.04) were associated with rehemorrhage within 1 year. A lower mRS score after previous hemorrhage (aOR 0.38 for a shift to a higher mRS score), Zabramski type I or V (OR 3.41), medulla or midbrain location (aOR 2.77), and multiple cerebral cavernous malformations (aOR 11.76) were associated with worsened neurological status at subsequent hemorrhage. The nomograms showed good accuracy and discrimination, with a C-index of 0.80 for predicting subsequent hemorrhage within 1 year and 0.71 for predicting neurological status after subsequent hemorrhage, which were maintained in cross-validation.

CONCLUSIONS An individualized approach to risk and severity assessment of BSCM rehemorrhage was feasible with clinical and imaging features.

Adult diffuse intrinsic pontine glioma: clinical, radiological, pathological, molecular features, and treatments of 96 patients

J Neurosurg 137:1628–1638, 2022

Unlike its pediatric counterpart, adult diffuse intrinsic pontine glioma (DIPG) remains largely unelucidated. In this study, the authors examined the clinical, radiological, pathological, molecular, and clinical aspects of 96 adult DIPGs.

METHODS The National Brain Tumor Registry of China (April 2013–December 2019) was used to collect data on radiologically diagnosed adult DIPG patients. Survival analysis was conducted using Kaplan-Meier curves and univariate and multivariate Cox regression. The chi-square test/Wilcoxon rank-sum test and multivariable logistic regression were used to examine the clinical and radiological characteristics of patients with long-term survival (LTS). Interaction analyses between clinical factors were also conducted.

RESULTS The median age at symptom onset was 33.5 years, and the median duration of symptoms was 4.5 months. The frequencies of H3K27M and IDH1 mutations were 37.2% and 26.5%, respectively. All adult DIPG patients had a median overall survival (OS) of 19.5 months, with 1-, 2-, and 3-year survival rates of 67.0%, 42.8%, and 36.0%, respectively. The median OS of 40 patients who did not undergo treatment was 13.4 months. Patients with H3K27M-mutant tumors had a poorer prognosis than those with IDH-mutant tumors (p < 0.001) and H3K27M(−)/IDH–wild-type tumors (p = 0.002), with a median OS of 11.4 months. The median OSs of patients with H3K27M-mutant tumors who received treatment and those who did not were 13.8 months and 7.5 months, respectively (p = 0.016). Among patients with and without a pathological diagnosis, H3K27M mutation (p < 0.001) and contrast enhancement on MRI (p = 0.003), respectively, imparted a worse prognosis. Treatments were the predictive factor for patients with H3K27M-mutant tumors (p = 0.038), whereas contrast enhancement on MRI was the prognostic factor for the H3K27M(−) group (p = 0.038). In addition, H3K27M mutation and treatment were significant predictors for patients with symptom duration ≤ 4 months (H3K27M, p = 0.020; treatment, p = 0.014) and tumors with no contrast enhancement (H3K27M, p = 0.003; treatment, p = 0.042). Patients with LTS were less likely to have cranial nerve palsy (p = 0.002) and contrast enhancement on MRI at diagnosis (p = 0.022).

CONCLUSIONS It is recommended that all adult DIPG patients undergo genomic testing for H3K27M and IDH mutations. Despite the low prevalence, additional study is needed to better characterize the efficacy of various treatment modalities in adults with DIPG.

Early Diagnosis and Surgical Intervention Within 3 Weeks From Symptom Onset Are Associated With Prolonged Survival of Patients With Glioblastoma

Neurosurgery 91:741–748, 2022

Glioblastoma (GBM) is a rapidly growing and most life-threatening malignant brain tumor. The significance of early treatment to the clinical outcomes of patients with GBM is unclear.

OBJECTIVE: To determine whether early diagnosis and surgery improve the preoperative and postoperative Karnofsky performance status (KPS) and prognosis of patients with GBM.

METHODS: Data of isocitrate dehydrogenase-wildtype patients with GBM treated at our institution between January 2010 and December 2019 were reviewed. Patients were classified into early or late diagnosis groups with a threshold of 14 days from initial symptoms. In addition, patients were divided into early, intermediate, and late surgery groups with thresholds of 21 and 35 days. Representative symptoms and patient prognoses were examined.

RESULTS: Of 153 patients, 72 and 81 were classified into the early and late diagnosis groups. The median tumor volume was significantly smaller in the former group. The proportion of patients with preoperative KPS scores ≥ 90 was 48.6%and 29.6% in the early and late diagnosis groups (P = .016). The early, intermediate, and late surgery groups included 43, 24, and 86 patients. The median overall survival was significantly longer in the early surgery group than in the late surgery group (28.4 vs 18.7 months, P = .006). Multivariate analysis demonstrated that significant predictors of shorter survival included extent of tumor resection (partial or biopsy), preoperative and postoperative KPS ≤ 60, and O6-methylguanine-DNA-methyltransferase promoter status (unmethylated).

CONCLUSION: Early diagnosis within 2 weeks and surgical interventions within 3 weeks from the symptom onset are associated with prolonged patient survival. Early GBM treatment will benefit patients with GBM.

Dumbbell-shaped pituitary adenomas: prognostic factors for prediction of tumor nondescent of the supradiaphragmal component from a multicenter series

J Neurosurg 137:609–617, 2022

Dumbbell-shaped pituitary adenomas (DSPAs) are a subgroup of macroadenomas with suprasellar extension that are characterized by a smaller diameter at the level of the diaphragma sellae opening compared with the supradiaphragmal tumor component (SDTC). Hence, DSPAs may be particularly prone to a nondescending suprasellar tumor component and risk for residual tumor or postoperative bleeding.

METHODS A multicenter retrospective cohort analysis of 99 patients with DSPA operated on via direct endoscopic endonasal transsphenoidal approach between 2011 and 2020 was conducted. Patient recruitment was performed at two tertiary care centers (Medical University of Vienna and University of Southern California) with expertise in endoscopic skull base surgery. DSPA was defined as having a smaller diameter at the level of the diaphragma sellae compared with the SDTC.

RESULTS On preoperative MRI, all DSPAs were macroadenomas (maximum diameter range 17–71 mm, volume range 2–88 cm 3 ). Tumor descent was found in 73 (74%) of 99 patients (group A), and nondescent in 26 (26%) of 99 patients (group B) intraoperatively. DSPAs in group A had a significantly smaller diameter (30 vs 42 mm, p < 0.001) and significantly smaller volume (10 vs 22 cm 3 , p < 0.001) than those in group B. The ratio of the minimum area at the level of the diaphragmal opening in comparison with the maximum area of the suprasellar tumor component (“neck-to-dome area”) was significantly lower in group A than in group B (1.7 vs 2.7, p < 0.001). Receiver operating characteristic curve analysis revealed an area under the curve of 0.75 (95% CI 0.63–0.87). At a cutoff ratio of 1.9, the sensitivity and specificity for a nondescending suprasellar tumor component were 77% and 34%, respectively.

CONCLUSIONS In the present study, the neck-to-dome area ratio was of prognostic value for prediction of intraoperative tumor nondescent in DSPAs operated on via a direct endonasal endoscopic approach. Pituitary adenoma SDTC nondescent carried the inherent risk of hemorrhagic transformation in all cases.

Dural arteriovenous fistulas without cortical venous drainage

J Neurosurg 136:942–950, 2022

Current evidence suggests that intracranial dural arteriovenous fistulas (dAVFs) without cortical venous drainage (CVD) have a benign clinical course. However, no large study has evaluated the safety and efficacy of current treatments and their impact over the natural history of dAVFs without CVD.

METHODS The authors conducted an analysis of the retrospectively collected multicenter Consortium for Dural Arteriovenous Fistula Outcomes Research (CONDOR) database. Patient demographics and presenting symptoms, angiographic features of the dAVFs, and treatment outcomes of patients with Borden type I dAVFs were reviewed. Clinical and radiological follow-up information was assessed to determine rates of new intracranial hemorrhage (ICH) or nonhemorrhagic neurological deficit (NHND), worsening of venous hyperdynamic symptoms (VHSs), angiographic recurrence, and progression or spontaneous regression of dAVFs over time.

RESULTS A total of 342 patients/Borden type I dAVFs were identified. The mean patient age was 58.1 ± 15.6 years, and 62% were women. The mean follow-up time was 37.7 ± 54.3 months. Of 230 (67.3%) treated dAVFs, 178 (77%) underwent mainly endovascular embolization, 11 (4.7%) radiosurgery alone, and 4 (1.7%) open surgery as the primary modality. After the first embolization, most dAVFs (47.2%) achieved only partial reduction in early venous filling. Multiple complementary interventions increased complete obliteration rates from 37.9% after first embolization to 46.7% after two or more embolizations, and 55.2% after combined radiosurgery and open surgery. Immediate postprocedural complications occurred in 35 dAVFs (15.2%) and 6 (2.6%) with permanent sequelae. Of 127 completely obliterated dAVFs by any therapeutic modality, 2 (1.6%) showed angiographic recurrence/recanalization at a mean of 34.2 months after treatment. Progression to Borden-Shucart type II or III was documented in 2.2% of patients and subsequent development of a new dAVF in 1.6%. Partial spontaneous regression was found in 22 (21.4%) of 103 nontreated dAVFs. Multivariate Cox regression analysis demonstrated that older age, NHND, or severe venous-hyperdynamic symptoms at presentation and infratentorial location were associated with worse prognosis. Kaplan-Meier curves showed no significant difference for stable/improved symptoms survival probability in treated versus nontreated dAVFs. However, estimated survival times showed better trends for treated dAVFs compared with nontreated dAVFs (288.1 months vs 151.1 months, log-rank p = 0.28). This difference was statistically significant for treated dAVFs with 100% occlusion (394 months, log-rank p < 0.001).

CONCLUSIONS Current therapeutic modalities for management of dAVFs without CVD may provide better symptom control when complete angiographic occlusion is achieved.

 

Deep Learning for Outcome Prediction in Neurosurgery

Neurosurgery 90:16–38, 2022

Deep learning (DL) is a powerful machine learning technique that has increasingly been used to predict surgical outcomes. However, the large quantity of data required and lack of model interpretability represent substantial barriers to the validity and reproducibility of DL models.

The objective of this study was to systematically review the characteristics of DL studies involving neurosurgical outcome prediction and to assess their bias and reporting quality.

Literature search using the PubMed, Scopus, and Embase databases identified 1949 records of which 35 studies were included. Of these, 32 (91%) developed and validated a DL model while 3 (9%) validated a pre-existing model. The most commonly represented subspecialty areas were oncology (16 of 35, 46%), spine (8 of 35, 23%), and vascular (6 of 35, 17%). Risk of bias was low in 18 studies (51%), unclear in 5 (14%), and high in 12 (34%), most commonly because of data quality deficiencies.

Adherence to transparent reporting of a multivariable prediction model for individual prognosis or diagnosis reporting standards was low, with a median of 12 transparent reporting of a multivariable prediction model for individual prognosis or diagnosis items (39%) per study not reported. Model transparency was severely limited because code was provided in only 3 studies (9%) and final models in 2 (6%).

With the exception of public databases, no study data sets were readily available. No studies described DL models as ready for clinical use. The use of DL for neurosurgical outcome prediction remains nascent. Lack of appropriate data sets poses a major concern for bias. Although studies have demonstrated promising results, greater transparency in model development and reporting is needed to facilitate reproducibility and validation.

Improved outcomes associated with maximal extent of resection for butterfly glioblastoma

Acta Neurochirurgica (2021) 163:1883–1894

Butterfly glioblastomas (bGBMs) are grade IV gliomas that infiltrate the corpus callosum and spread to bilateral cerebral hemispheres. Due to the rarity of cases, there is a dearth of information in existing literature. Herein, we evaluate clinical and genetic characteristics, associated predictors, and survival outcomes in an institutional series and compare them to a national cohort.

Methods We identified all adult patients with bGBM treated at Brigham & Women’s Hospital (2008–2018). The National Cancer Database (NCDB) was also queried for bGBM patients. Survival was analyzed with Kaplan–Meier methods, and Cox models were built to assess for predictive factors.

Results Of 993 glioblastoma patients, 62 cases (6.2%) of bGBM were identified. Craniotomy for resection was attempted in 26 patients (41.9%), with a median volumetric extent of resection (vEOR) of 72.3% (95% confidence interval [95%CI] 58.3–82.1). The IDH1 R132H mutation was detected in two patients (3.2%), and MGMT promoter was methylated in 55.5% of the assessed cases. In multivariable regression, factors predictive of longer OS were increased vEOR, MGMT promoter methylation, and receipt of adjuvant therapy. Median OS for the resected cases was 11.5 months (95%CI 7.7–18.8) vs. 6.3 (95%CI 5.1–8.9) for the biopsied. Of 21,353 GBMs, 719 (3.37%) bGBM patients were identified in the NCDB. Resection was more likely to be pursued in recent years, and GTR was independently associated with prolonged OS (p < 0.01).

Conclusion Surgical resection followed by adjuvant chemoradiation is associated with significant survival gains and should be pursued in carefully selected bGBM patients.

The impact of statin therapy after surgical or endovascular treatment of cerebral aneurysms

J Neurosurg 133:182–189, 2020

Cerebral aneurysms represent the most common cause of spontaneous subarachnoid hemorrhage. Statins are lipid-lowering agents that may expert multiple pleiotropic vascular protective effects. The authors hypothesized that statin therapy after coil embolization or surgical clipping of cerebral aneurysms might improve clinical outcomes.

METHODS This was a retrospective cohort study using the National Health Insurance Service–National Sample Cohort Database in Korea. Patients who underwent coil embolization or surgical clipping for cerebral aneurysm between 2002 and 2013 were included. Based on prescription claims, the authors calculated the proportion of days covered (PDC) by statins during follow-up as a marker of statin therapy. The primary outcome was a composite of the development of stroke, myocardial infarction, and all-cause death. Multivariate time-dependent Cox regression analyses were performed.

RESULTS A total of 1381 patients who underwent coil embolization (n = 542) or surgical clipping (n = 839) of cerebral aneurysms were included in this study. During the mean (± SD) follow-up period of 3.83 ± 3.35 years, 335 (24.3%) patients experienced the primary outcome. Adjustments were performed for sex, age (as a continuous variable), treatment modality, aneurysm rupture status (ruptured or unruptured aneurysm), hypertension, diabetes mellitus, household income level, and prior history of ischemic stroke or intracerebral hemorrhage as time-independent variables and statin therapy during follow-up as a time-dependent variable. Consistent statin therapy (PDC > 80%) was significantly associated with a lower risk of the primary outcome (adjusted hazard ratio 0.34, 95% CI 0.14–0.85).

CONCLUSIONS Consistent statin therapy was significantly associated with better prognosis after coil embolization or surgical clipping of cerebral aneurysms.

 

Characterizing tumor invasiveness of glioblastoma using multiparametric magnetic resonance imaging

J Neurosurg 132:1465–1472, 2020

The objective of this study was to characterize the abnormalities revealed by diffusion tensor imaging (DTI) using MR spectroscopy (MRS) and perfusion imaging, and to evaluate the prognostic value of a proposed quantitative measure of tumor invasiveness by combining contrast-enhancing (CE) and DTI abnormalities in patients with glioblastoma.

METHODS Eighty-four patients with glioblastoma were recruited preoperatively. DTI was decomposed into isotropic (p) and anisotropic (q) components. The relative cerebral blood volume (rCBV) was calculated from the dynamic susceptibility contrast imaging. Values of N-acetylaspartate, myoinositol, choline (Cho), lactate (Lac), and glutamate + glutamine (Glx) were measured from multivoxel MRS and normalized as ratios to creatine (Cr). Tumor regions of interest (ROIs) were manually segmented from the CE T1-weighted (CE-ROI) and DTI-q (q-ROI) maps. Perfusion and metabolic characteristics of these ROIs were measured and compared. The relative invasiveness coefficient (RIC) was calculated as a ratio of the characteristic radii of CE-ROI and q-ROI. The prognostic significance of RIC was tested using Kaplan-Meier and multivariate Cox regression analyses.

RESULTS The Cho/Cr, Lac/Cr, and Glx/Cr in q-ROI were significantly higher than CE-ROI (p = 0.004, p = 0.005, and p = 0.007, respectively). CE-ROI had significantly higher rCBV values than q-ROI (p < 0.001). A higher RIC was associated with worse survival in a multivariate overall survival (OS) model (hazard ratio [HR] 1.40, 95% confidence interval [CI] 1.06–1.85, p = 0.016) and progression-free survival (PFS) model (HR 1.55, 95% CI 1.16–2.07, p = 0.003). An RIC cutoff value of 0.89 significantly predicted shorter OS (median 384 vs 605 days, p = 0.002) and PFS (median 244 vs 406 days, p = 0.001).

CONCLUSIONS DTI-q abnormalities displayed higher tumor load and hypoxic signatures compared with CE abnormalities, whereas CE regions potentially represented the tumor proliferation edge. Integrating the extents of invasion visualized by DTI-q and CE images into clinical practice may lead to improved treatment efficacy.

A novel proposed grading system for cerebellar arteriovenous malformations

J Neurosurg 132:1105–1115, 2020

The objective of this study was to evaluate the existing Spetzler-Martin (SM), Spetzler-Ponce (SP), and Lawton-Young (LY) grading systems for cerebellar arteriovenous malformations (AVMs) and to propose a new grading system to estimate the risks associated with these lesions.

METHODS Data for patients with cerebellar AVMs treated microsurgically in two tertiary medical centers were retrospectively reviewed. Data from patients at institution 1 were collected from September 1999 to February 2013, and at institution 2 from October 2008 to October 2015. Patient outcomes were classified as favorable (modified Rankin Scale [mRS] score 0–2) or poor (mRS score 3–6) at the time of discharge. Using chi-square and logistic regression analysis, variables associated with poor outcomes were assigned risk points to design the proposed grading system. The proposed system included neurological status prior to treatment (poor, +2 points), emergency surgery (+1 point), age > 60 years (+1 point), and deep venous drainage (deep, +1 point). Risk point totals of 0–1 comprised grade 1, 2–3 grade 2, and 4–5 grade 3.

RESULTS A total of 125 cerebellar AVMs of 1328 brain AVMs were reviewed in 125 patients, 120 of which were treated microsurgically and included in the study. With our proposed grading system, we found poor outcomes differed significantly between each grade (p < 0.001), while with the SM, SP, and LY grading systems they did not (p = 0.22, p = 0.25, and p = 1, respectively). Logistic regression revealed grade 2 had 3.3 times the risk of experiencing a poor outcome (p = 0.008), while grade 3 had 9.9 times the risk (p < 0.001). The proposed grading system demonstrated a superior level of predictive accuracy (area under the receiver operating characteristic curve [AUROC] of 0.72) compared with the SM, SP, and LY grading systems (AUROC of 0.61, 0.57, and 0.51, respectively).

CONCLUSIONS The authors propose a novel grading system for cerebellar AVMs based on emergency surgery, venous drainage, preoperative neurological status, and age that provides a superior prognostication power than the formerly proposed SM, SP, and LY grading systems. This grading system is clinically predictive of patient outcomes and can be used to better guide vascular neurosurgeons in clinical decision-making.

 

A novel proposed grading system for cerebellar arteriovenous malformations

J Neurosurg 132:1105–1115, 2020

The objective of this study was to evaluate the existing Spetzler-Martin (SM), Spetzler-Ponce (SP), and Lawton-Young (LY) grading systems for cerebellar arteriovenous malformations (AVMs) and to propose a new grading system to estimate the risks associated with these lesions.

METHODS Data for patients with cerebellar AVMs treated microsurgically in two tertiary medical centers were retrospectively reviewed. Data from patients at institution 1 were collected from September 1999 to February 2013, and at institution 2 from October 2008 to October 2015. Patient outcomes were classified as favorable (modified Rankin Scale [mRS] score 0–2) or poor (mRS score 3–6) at the time of discharge. Using chi-square and logistic regression analysis, variables associated with poor outcomes were assigned risk points to design the proposed grading system. The proposed system included neurological status prior to treatment (poor, +2 points), emergency surgery (+1 point), age > 60 years (+1 point), and deep venous drainage (deep, +1 point). Risk point totals of 0–1 comprised grade 1, 2–3 grade 2, and 4–5 grade 3.

RESULTS A total of 125 cerebellar AVMs of 1328 brain AVMs were reviewed in 125 patients, 120 of which were treated microsurgically and included in the study. With our proposed grading system, we found poor outcomes differed significantly between each grade (p < 0.001), while with the SM, SP, and LY grading systems they did not (p = 0.22, p = 0.25, and p = 1, respectively). Logistic regression revealed grade 2 had 3.3 times the risk of experiencing a poor outcome (p = 0.008), while grade 3 had 9.9 times the risk (p < 0.001). The proposed grading system demonstrated a superior level of predictive accuracy (area under the receiver operating characteristic curve [AUROC] of 0.72) compared with the SM, SP, and LY grading systems (AUROC of 0.61, 0.57, and 0.51, respectively).

CONCLUSIONS The authors propose a novel grading system for cerebellar AVMs based on emergency surgery, venous drainage, preoperative neurological status, and age that provides a superior prognostication power than the formerly proposed SM, SP, and LY grading systems. This grading system is clinically predictive of patient outcomes and can be used to better guide vascular neurosurgeons in clinical decision-making.

 

Short-term versus long-term outcomes of microvascular decompression for hemifacial spasm

Acta Neurochirurgica (2019) 161:2027–2033

Microvascular decompression (MVD) is a useful treatment for hemifacial spasm (HFS), but the postoperative course is extremely diverse. The purpose of this study was to compare short- and long-term outcomes, find the earliest optimal time for determining the long-term outcomes, and investigate the prognostic factors involved in the outcomes over time.

Methods From July 2004 to January 2015, 1341 patients who underwent MVD for HFS were enrolled. Information on clinical features, operative findings, and surgical outcomes over time were collected by performing a review of electronic medical records, and their relationships were analyzed. The outcomes of MVD at 1, 3, 6, and 9 months were individually compared against those at > 12 months after surgery.

Results The mean follow-up period after surgery was 44.9 months (median, 36.8 months; range, 12.0–156.6 months). The overall improvement rate for the 1341 patients was 89.0%. Individual postoperative outcomes at 6 and 9 months showed no differences with those at > 12 months after surgery. Furthermore, in the uni- and multi-variable analyses, patients in whom the offending vessels were intraoperatively determined to be veins showed bad outcomes at 6, 9, and > 12 months (p = 0.048, p = 0.004, and p = 0.003, respectively). Patients with intraoperative indentation on the facial nerve showed good outcomes at 6, 9, and > 12 months (p = 0.005, p = 0.039, and p = 0.020, respectively). Patients with delayed facial palsy after surgery showed better outcomes at 6, 9, and > 12 months (p = 0.002, p = 0.003, and p = 0.028, respectively).

Conclusions Short- and long-term outcomes of MVD in patients with HFS manifested differently, but the outcomes at 6 and 9 months showed similarities with those at > 12 months. In patients in whom the intraoperatively detected offending vessel was not a vein, and in patients with intraoperative indentation on the facial nerve and postoperative delayed facial palsy, good outcomes could be predicted after 6 months of surgery.

Transcortical insular glioma resection: clinical outcome and predictors

J Neurosurg 131:706–716, 2019

Insular lobe gliomas continue to challenge neurosurgeons due to their complex anatomical position. Transcortical and transsylvian corridors remain the primary approaches for reaching the insula, but the adoption of one technique over the other remains controversial. The authors analyzed the transcortical approach of resecting insular gliomas in the context of patient tumor location based on the Berger-Sinai classification, achievable extents of resection (EORs), overall survival (OS), and postsurgical neurological outcome.

METHODS The authors studied 255 consecutive cases of insular gliomas that underwent transcortical tumor resection in their division. Tumor molecular pathology, location, EOR, postoperative neurological outcome for each insular zone, and the accompanying OS were incorporated into the analysis to determine the value of this surgical approach.

RESULTS Lower-grade insular gliomas (LGGs) were more prevalent (63.14%). Regarding location, giant tumors (involving all insular zones) were most prevalent (58.82%) followed by zone I+IV (anterior) tumors (20.39%). In LGGs, tumor location was an independent predictor of survival (p = 0.003), with giant tumors demonstrating shortest patient survival (p = 0.003). Isocitrate dehydrogenase 1 (IDH1) mutation was more likely to be associated with giant tumors (p < 0.001) than focal tumors located in a regional zone. EOR correlated with survival in both LGG (p = 0.001) and higher-grade glioma (HGG) patients (p = 0.008). The highest EORs were achieved in anterior-zone LGGs (p = 0.024). In terms of developing postoperative neurological deficits, patients with giant tumors were more susceptible (p = 0.038). Postoperative transient neurological deficit was recorded in 12.79%, and permanent deficit in 15.70% of patients. Patients who developed either transient or permanent postsurgical neurological deficits exhibited poorer survival (p < 0.001).

CONCLUSIONS The transcortical surgical approach can achieve maximal tumor resection in all insular zones. In addition, the incorporation of adjunct technologies such as multimodal brain imaging and mapping of cortical and subcortical eloquent brain regions into the transcortical approach favors postoperative neurological outcomes, and prolongs patient survival.

Transcortical insular glioma resection: clinical outcome and predictors

J Neurosurg 131:706–716, 2019

OBJECTIVE Insular lobe gliomas continue to challenge neurosurgeons due to their complex anatomical position. Transcortical and transsylvian corridors remain the primary approaches for reaching the insula, but the adoption of one technique over the other remains controversial. The authors analyzed the transcortical approach of resecting insular gliomas in the context of patient tumor location based on the Berger-Sinai classification, achievable extents of resection (EORs), overall survival (OS), and postsurgical neurological outcome.

METHODS The authors studied 255 consecutive cases of insular gliomas that underwent transcortical tumor resection in their division. Tumor molecular pathology, location, EOR, postoperative neurological outcome for each insular zone, and the accompanying OS were incorporated into the analysis to determine the value of this surgical approach.

RESULTS Lower-grade insular gliomas (LGGs) were more prevalent (63.14%). Regarding location, giant tumors (involving all insular zones) were most prevalent (58.82%) followed by zone I+IV (anterior) tumors (20.39%). In LGGs, tumor location was an independent predictor of survival (p = 0.003), with giant tumors demonstrating shortest patient survival (p = 0.003). Isocitrate dehydrogenase 1 (IDH1) mutation was more likely to be associated with giant tumors (p < 0.001) than focal tumors located in a regional zone. EOR correlated with survival in both LGG (p = 0.001) and higher-grade glioma (HGG) patients (p = 0.008). The highest EORs were achieved in anterior-zone LGGs (p = 0.024). In terms of developing postoperative neurological deficits, patients with giant tumors were more susceptible (p = 0.038). Postoperative transient neurological deficit was recorded in 12.79%, and permanent deficit in 15.70% of patients. Patients who developed either transient or permanent postsurgical neurological deficits exhibited poorer survival (p < 0.001).

CONCLUSIONS The transcortical surgical approach can achieve maximal tumor resection in all insular zones. In addition, the incorporation of adjunct technologies such as multimodal brain imaging and mapping of cortical and subcortical eloquent brain regions into the transcortical approach favors postoperative neurological outcomes, and prolongs patient survival.

 

Prospective validation of a molecular prognostication panel for clival chordoma

J Neurosurg 130:1528–1537, 2019

There are currently no reliable means to predict the wide variability in behavior of clival chordoma so as to guide clinical decision-making and patient education. Furthermore, there is no method of predicting a tumor’s response to radiation therapy.

METHODS A molecular prognostication panel, consisting of fluorescence in situ hybridization (FISH) of the chromosomal loci 1p36 and 9p21, as well as immunohistochemistry for Ki-67, was prospectively evaluated in 105 clival chordoma samples from November 2007 to April 2016. The results were correlated with overall progression-free survival after surgery (PFSS), as well as progression-free survival after radiotherapy (PFSR).

RESULTS Although Ki-67 and the percentages of tumor cells with 1q25 hyperploidy, 1p36 deletions, and homozygous 9p21 deletions were all found to be predictive of PFSS and PFSR in univariate analyses, only 1p36 deletions and homozygous 9p21 deletions were shown to be independently predictive in a multivariate analysis. Using a prognostication calculator formulated by a separate multivariate Cox model, two 1p36 deletion strata (0%–15% and > 15% deleted tumor cells) and three 9p21 homozygous deletion strata (0%–3%, 4%–24%, and ≥ 25% deleted tumor cells) accounted for a range of cumulative hazard ratios of 1 to 56.1 for PFSS and 1 to 75.6 for PFSR.

CONCLUSIONS Homozygous 9p21 deletions and 1p36 deletions are independent prognostic factors in clival chordoma and can account for a wide spectrum of overall PFSS and PFSR. This panel can be used to guide management after resection of clival chordomas.

 

Hemorrhagic burden in poor-grade aneurysmal subarachnoid hemorrhage

Acta Neurochirurgica (2019) 161:791–797

Volumetric assessment of aneurysmal bleeding has been evaluated in few studies and emerged as a promising outcome predictor. There is a lack of studies evaluating its impact in the poor-grade population.

Methods Retrospective review of 63 consecutive poor-grade aneurysmal subarachnoid hemorrhage (aSAH) patients, defined as grade IV and V according to theWorld Federation of Neurological Surgeons (WFNS) classifications. Global intracranial bleeding volume was calculated with its subarachnoid, intracerebral (ICH), and intraventricular (IVH) portions by means of analytical software. Univariate and multivariate analyses were performed in order to identify independent predictors of outcome. Good outcome was defined as modified Rankin Scale (mRS) 0–2 and mortality as mRS 6. The cutoff values of bleeding volumes were derived by receiver operating curve (ROC) analysis.

Results Mean follow-up was of 12.5 (± 1.5) months. Thirty (47.7%) patients achieved good outcome, whereas 19 (30.2) patients out of 63 died. Global intracranial bleeding resulted as an independent predictor of good outcome (cutoff 24 mL). Furthermore, ICH relative percentage of global volume (10% of total) and pure SAH (64% of total) emerged respectively as independent predictors of worsened and improved outcome. Global bleeding volume (cutoff 51 mL) along with global cerebral edema showed to independently predict mortality in the examined poor-grade aSAH population.

Conclusions Volumetric assessment of aneurysmal bleeding has the potential for identifying cutoff values that independently predict outcome. Further insights into the relative importance of different bleeding volumes may be implicated in better tailoring the management of this dismal aSAH population.

Prognosis of Symptoms and Complications After Microvascular Decompression for Hemifacial Spasm

World Neurosurg. (2018) 118:e557-e561

The aim of this study was to identify potential prognostic factors of hemifacial spasm (HFS) after microvascular decompression (MVD), to establish the appropriate way to tackle postprocedure symptoms and complications (PPSCs), and to find the incidence and duration of PPSCs.

METHODS: Two hundred and forty-eight patients with HFS were monitored between December 2009 and December 2014. The mean follow-up duration was 24 months (range, 6e67 months). We divided patients based on their PPSC status and investigated the following factors: age, sex, spasm side, facial nerve block before MVD (botulinum toxin treatment), acupuncture before MVD, duration of HFS, hypertension, diabetes, hepatitis B virus (HBV) infection status, herpes simplex virus infection status, smoking status and alcohol use, offending vessels, Chiari malformation, electrophysiologic monitoring results, and postoperative HFS. Univariable analysis and multivariate logistic regression were used to find potential risk factors. Kaplan-Meier analysis was used to show the duration of postprocedure facial palsy.

RESULTS: Age (odds ratio [OR], 1.037; 95% confidence interval [CI], 1.004e1.072; P [ 0.03) and HBV status (OR, 18.256; 95% CI, 2.723e122.415; P [ 0.03) were positive predictors of PPSCs. Postoperative HFS (OR, 0.249; 95% CI, 0.084e0.0739; P [ 0.012) may be a protective factor for postprocedure facial palsy. Most PPSCs related to cranial nerves recovered spontaneously in 3 months. Infections and cerebrospinal fluid leakages were controlled by medical intervention in 1e2 weeks. The permanent complication rate was only 4.8%.

CONCLUSIONS: Although the incidence of PPSCs after MVD is very high, most PPSCs related to cranial nerves recovered spontaneously in several days. Permanent complications after MVD for HFS are rare. Age may relate to the occurrence of PPSCs, and postoperative HFS may be a protective factor for patients with facial palsy after MVD.

Intramedullary ependymoma: long-term outcome after surgery

Acta Neurochirurgica (2018) 160:439–447

Overall (OS) and progression-free survival (PFS) of patients undergoing spinal ependymoma resection has been frequently reported. Contrarily, OS and PFS of purely intramedullary ependymomas have not been clearly determined yet.

Methods The data of 37 patients undergoing resection of an intramedullary ependymoma (IE) from January 2000 to December 2016 were analysed retrospectively.

Results The mean age was 46 years. The male:female ratio was 24:13. The median duration of symptoms was 12 months. Sixtytwo per cent of ependymomas were in the cervical, 24% in the thoracic, and 14% in the conus region in our series. The median volume was 1.3 ml. A syrinx was found in 49%and a cyst in 32%. GTR was achieved in 89%, STR in three (8%), and PR in one patient (3%). Median follow-up was 114 months. PFS was 87%, 82%, and 82%at 5, 10, and 15 years, respectively. OS was 97%, 88%, and 63% at 5, 10, and 15 years, respectively. There was a significant difference in PFS depending on the extent of resection and in OS depending on the pre-operative clinical status. There was no significant difference in OS and PFS regarding the other examined influencing factors.

Conclusion GTR resection was the most important factor influencing PFS. According to our results OS of IEs is much worse than that of spinal ependymomas. Our analysis confirms that patients with good pre-operative (McCormick grade 1 and 2) clinical status have significantly better OS than patients with McCormick grade 3 and higher.